Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen that rarely causes disease in healthy people, but is a significant problem for critically ill or immunocompromised individuals. Infection is a major problem in individuals who have cystic fibrosis (CF), where P. aeruginosa is a causative agent in the progressive loss of lung function resulting from recurrent and chronic respiratory tract infections with the bacterium. Others at risk from Pseudomonas aeruginosa infection include patients on mechanical ventilators, neutropenic cancer patients, and burn patients. P. aeruginosa is often resistant to most antibiotics and new treatment approaches are greatly needed.
The type III secretion system is an important virulence factor determinant in that it inhibits host defense system. Upon activation, the type III secretion apparatus translocates toxins into the cytoplasm of the host cell, resulting in cell rounding, lifting, and cell death by necrosis or apoptosis. PcrV is an essential component of the type III secretion apparatus. Blocking of PcrV can inhibit toxin secretion through the Type III secretion system, thereby allowing natural clearance mechanisms to eliminate the bacteria. PcrV is conserved in all P. aeruginosa strains tested thus far.
Antibodies to the PcrV antigen of Pseudomonas are known in the art. The current invention provides improved PcrV antibodies, e.g., for the treatment of Pseudomonas aeruginosa infections.